Chromosomal abnormalities, translocations, inversions and deletions are nonrandomly associated with certain types of human leukemias and lymphomas (Yunis, J., 1982, Science 221:227-236). In T-cell tumors, many such abnormalities involve the T-cell receptor alpha locus (TCR alpha) at chromosome band 14 q11 (Croce, C. M., et al., 1985, Science 227:1044-1047; Isobe, M., et al., 1988, Proc. Natl. Acad. Sci. USA 85:3933-3937; Zech, L., et al., 1984, Nature 308:858-860; Erickson, J., et al., 1985, Science 229:784-786). The TCR delta locus was identified between the 5' portion of the alpha chain J segments and the V alpha segments (Chien, Y., et al., 1987, Nature 327:667-682; Hata, S., et al., 1987, Science 238:678-681). By means of somatic cell hybrids and molecular cloning of the entire delta locus (Isobe, M., et al., 1988, Proc. Natl. Acad. Sci. USA 85:3933-3937; Boehm, T., et al., 1988, EMBO J. 7:385-394), the direct involvement of the J delta-D delta segments in t(11;14) and t(8;14) chromosome translocations in T-cell malignancies was demonstrated (Isobe, M., et al., 1988, Proc. Natl. Acad. Sci. USA 85:3933-3937; Boehm, T., et al., 1988, EMBO J. 7:385-394; Boehm, T., et al., 1988, EMBO J. 7:2011-2017).
The t(10;14) (q24; q11) chromosome translocation has been described in acute T-cell leukemias and high-grade T-cell lymphomas (Hecht, F., et al., 1984, Science 226:1445-1446; Dube, I. D., et al., 1986, Blood 67:1181-1184; Kagan, J., et al., 1987, Proc. Natl. Acad. Sci. USA 84:4543-4546). Cells derived from three different patients with acute T-cell leukemia were analyzed and the breakpoint in this translocation was found within the TCR alpha locus in the region between the C alpha and V alpha genes on chromosome 14 (Kagan, J., et al., 1987, Proc. Natl. Acad. Sci. USA 84:4543-4546). Isobe, et al., 1988, Proc. Natl. Acad. Sci. USA, pp. 3933-3937, reported that in one case of T-cell leukemia/lymphoma carrying the t(10;14) (q24; q11) translocation, the TCR delta locus was found to be rearranged.
The only diagnostic test for the t(10;14) translocation now available is cytogenetic analysis which is labor intensive, expensive, and often unsuccessful. Thus, there is a need in the art for further definition of the chromosome translocation breakpoint sites involved in T-cell malignancies so that simpler and more rapid tests can be devised for diagnosis of these diseases.